The primary goal of this application is to establish a foundation of basic scientists with translational research projects studying developmental mechanisms underlying children's disease by establishing the Center for Pediatric Research. The origin of many pediatric diseases is from altered developmental programming related to the processes of cell proliferation, morphogenesis, migration, differentiation, and programmed death. These developmental processes are at the root of pediatric disease and are disrupted through genetic disorders, aberrant fetal programming, altered growth & development, and environmental pressures. Our multidisciplinary Center applies genetic, biochemical, cell, and molecular approaches across several model organisms to characterize alterations during development as they pertain to pediatric diseases and disorders. Projects from five outstanding early-stage investigators with the potential to become competitive scientists at the national level have been selected for this application. Center success will be achieved through the following Aims: 1) create a supportive environment for the training and mentorship of basic scientists studying developmental processes related to pediatric disease mechanisms; 2) utilize new and existing resources that will enhance pediatric research; 3) enhance communication mechanisms to promote and initiate clinical and translational research projects; 4) expand training and learning opportunities in the biology of pediatric disease and development; and 5) evaluate success of the Center. Through these Aims, the Center for Pediatric Research will develop a strong foundation in basic and translational research by fostering a collaborative environment for scientists and physicians. Strengthened by our institution's strong commitment to children's medicine, we propose that the Center will enhance pediatric research efforts in South Dakota.